Inhibition by nitric oxide of the repair protein, O6-DNA-methyltransferase

Abstract

Nitric oxide (NO) has been shown to be involved in a number of physiological processes. In the presence of oxygen, this reactive diatomic molecule is capable of generating reactive nitrogen oxide species (NO_x) which possess both nitrosating and oxidizing ability for various substrates, including certain biological macromolecules. This report shows the inhibition of the DNA repair protein, (O⁶-methylguanine-DNA-methyltransferase, by Et₂N[N(O)NO]Na (DEA/NO), a compound which decomposes with concurrent release of NO. The inhibition of the purified transferase activity by NO was dose- and time-dependent and the extent of inhibition by DEA/NO corresponded to the total quantity of NO released. This inhibitory effect by NO was also demonstrated to be reversible over time. The reaction of the NO released from DEA/NO with cysteine under aerobic conditions resulted in the formation of an S-nitrosothiol adduct, suggesting that a similar adduct could be responsible for the inactivation.